NMDAR-dependent LTP enhances proliferation of NPCs in the DG.

<p>(<i>A</i>) The induction of LTP in the hippocampal DG requires activation of NMDARs. A stable basal level of fEPSPs was obtained by electrical stimulation of MPP (0.05 Hz) from the DG of anesthetized rats and LTP was induced by application of sTPS through the same stimulation electrode. Representative traces of fEPSP on the left were averages of all individual recordings before and after the establishment of LTP. Systemic application of the competitive NMDAR antagonist CPP (10 mg/kg) prevented the induction of LTP (CPP+sTPS), without affecting basal level of fEPSP (0.05 Hz+CPP). (<i>B</i>) LTP increases the total numbers of PCNA-positive immature neurons in the DG. Representative images from coronal sections from non-LTP (0.05 Hz+ saline) and LTP-induced (LTP) rats co-stained with PCNA (red) and DAPI (blue) in the DG area. Examples of doubled-stained cells in boxed areas were shown in higher magnification on the right panels. Bar graph on the right summarizes data from various groups, suggesting enhancement of proliferation by LTP induction. Note CPP pretreatment alone (0.05 Hz+CPP) has no effect on intrinsic proliferation, but prevented LTP-promoted NPC proliferation (CPP+sTPS). **p<0.01, n = 8 or 9. Statistical analysis was performed with One Way ANOVA. <i>Post hoc</i> testing revealed a significant difference between the LTP group and other three groups. Data are mean ± SEM. significantly different from each other.